Molecular Dynamics Simulations of PIP2 and PIP3 in Lipid Bilayers: Determination of Ring Orientation, and the Effects of Surface Roughness on a Poisson-Boltzmann Description
Molecular Dynamics Simulations of PIP2 and PIP3 in Lipid Bilayers: Determination of Ring Orientation, and the Effects of Surface Roughness on a Poisson-Boltzmann Description
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DOI：
10.1016/j.bpj.2009.04.037
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发表时间：
2009-07-08
影响因子：
3.4
通讯作者：
Pastor, Richard W.
中科院分区：
文献类型：
--
作者：
Li, Zheng;Venable, Richard M.;Pastor, Richard W.
分子动力学（MD）模拟磷脂酰肌醇（4，5）-二磷酸（PIP 2）和磷脂酰肌醇（3，4，5）-三磷酸（PIP 3）在1-棕榈酰-2-油酰磷脂酰胆碱（POPC）双层中的作用表明，肌醇环相对于双层表面倾斜约40度，而POPC的P-N矢量为17度。对于环扭转（类似于飞机的滚转）获得了多个最小值。在PIP 2和PIP 3的位置1处的磷酸盐在由POPC的磷酸盐形成的平面的1埃内;周围壳中的脂质被压低0.5-0.8埃，但除此之外磷酸肌醇基本上不扰动双层。对于类似于26沃茨/脂质的系统，离子分布的有限尺寸伪影是明显的，但是，基于水相增加四倍的模拟，磷酸肌醇的位置和取向没有显示出显著的尺寸效应。从泊松-玻尔兹曼（PB）计算评估的静电势显示出对电势高度和环取向的强烈依赖性，在-25 mV表面上的最大值（对于PIP 2为17.1 +/-0.1埃，对于PIP 3为19.4 +/-0.3埃）发生在MD的最多填充取向附近。这些表面远高于对带负电荷的细胞膜估计的10埃的背景高度，如对参与细胞信号传导的脂质所预期的。PB计算微观平坦的双层产生类似的最大值的MD为基础的（微观粗糙）系统，但显示不太精细的结构，并没有清楚地表明最可能的地区。与pentalysin相互作用的静电自由能也是类似的粗糙和平坦的系统。这些结果支持的实用程序的刚性/平面双层模型的PB为基础的研究PIP 2和PIP 3，只要方向是明智的选择。
Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5) -trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted similar to 40 degrees with respect to the bilayer surface, as compared with 17 degrees for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Angstrom of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 angstrom, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of similar to 26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the -25 mV surfaces (17.1 +/- 0.1 angstrom for PIP2 and 19.4 +/- 0.3 angstrom for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 angstrom estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen.